External skin care preparation

ABSTRACT

An external skin care preparation comprising a compound represented by the following general formula (I) or (II), or a salt thereof: ##STR1## wherein R 1  means an aliphatic hydrocarbon group having 9-25 carbon atoms, A and B denote specific groups respectively, R 6  and R 7  are individually an aliphatic hydrocarbon group having 10-26 carbon atoms, and R 8  denotes a group --CH 2  CH 2  OH, --CH 2  COOH or --COCH 3 .

This is a division of application Ser. No. 07/163,835, filed on Mar. 3,1988, now U.S. Pat. No. 4,985,547.

BACKGROUND OF THE INVENTION

1) Field of the Invention

This invention relates to an external skin care preparation, and morespecifically to an external skin care preparation which can enhance thewater-retaining ability of the horny layer and improve skin roughness.

2) Description of the Related Art

The water content of the horny layer has already been known to becritical for imparting moisture to the skin to maintain the skinsmoothness and softness. The retention of water is said to rely upon awater-soluble component contained in the horny layer, namely, a freeamino acid, organic acid, urea or inorganic ions. These materials havebeen incorporated either singly or in combination in medical externalskin care preparations or cosmetic preparations with a view towardimproving or avoiding skin roughness.

Besides, many humectants having high affinity with water have also beendeveloped and have been used for similar purposes.

However, these humectants remain on the skin surface when they areapplied to the skin, so that they serve to supply water to horny layer.Moreover, their effects are temporary and they are not such that canimprove the water-retaining ability of the horny layer and can alsoavoid or cure skin roughness substantially.

SUMMARY OF THE INVENTION

Under the above circumstances, the present inventors have carried out anextensive investigation with a view toward solving the above problems.As a result, it has been found that a compound represented by thefollowing general formula (I) or (II) or a salt thereof shows effects inimproving the water-retaining ability of the horny layer significantlyand the combined use of a surfactant with the compound or salt canenhance the effects further, leading to completion of this invention.

General formula (I) ##STR2## wherein R¹ means an aliphatic hydrocarbongroup having 9-25 carbon atoms, A denotes a group --(--CH₂)_(l) OH (l:integer of 3-6), a group ##STR3## (X¹, X², X³ : H, C₁₋₅ -alkyl orhydroxyalkyl, individually), a group --(--CH₂ CH₂ O)_(m) H (m: integerof at least 2), a group ##STR4## (Y: H or alkali metal; R² : H, --CH₃,##STR5## (CH₃)₂ CHCH₂ --, C₂ H₅ (CH₃)CHCH₂ --, HOCH₂ --, CH₃ (HO)CH--,CH₃ SCH₂ CH₂ --, YOCOCH₂ --, YOCOCH₂ CH₂ --, ##STR6## or a group --CH₂CH₂ OR³ [R³ sugar residuum or group ##STR7## (Z¹, Z², Z³ : H,straight-chain or branched C₁₋₆ -alkyl, or aralkyl)], and B stands for agroup ##STR8## [R⁴ : H, sugar residuum, group ##STR9## (Z¹, Z², Z³ : thedefined above) or group --(--CH₂ CH₂ O)_(n) H (n: integer of at least1); R⁵ : C₈₋₂₈ -aliphatic hydrocarbon group] or a group ##STR10## (R⁵ :as defined above), with a proviso that X¹, X², X³ and R⁴ do not mean Hat the same time. General formula (II) ##STR11## wherein R⁶ and R⁷ meanindividually an aliphatic hydrocarbon group having 10-26 carbon atomsand R⁸ denotes a group --CH₂ CH₂ OH, --CH₂ COOH or --COCH₃.

In one aspect of the invention, there is thus provided an external skincare preparation comprising a compound represented by the formula (I) or(II) or a salt thereof. The external skin care preparation mayadditionally contain a surfactant.

In another aspect of the invention, there is also provided a glycolipidderivative represented by the following general formula (Ie'): ##STR12##wherein R¹ means an aliphatic hydrocarbon group having 9-25, R⁵¹ denotesan aliphatic hydrocarbon group having 10-26, and R³³ and R³⁴ areindividually H or sugar residuum, with a proviso that R³³ and R³⁴ do notmean H at the same time.

Although details of the mechanism of action of the compound representedby the formula (I) or (II) or a salt thereof in the external skin carepreparation of this invention has not been elucidated fully, it appearsto reconstruct lipid membranes between horny cells to allow the hornylayer to exhibit its water-retaining function.

Owing to the inclusion of the compound (I) or (II) or a salt thereofhaving such an action, the external skin care preparation according tothe present invention can exhibit excellent effects for the improvementand prevention of skin roughness.

The above and other objects, features and advantages of the presentinvention will become apparent from the following description and theappended claims.

DETAILED DESCRIPTION OF THE INVENTION

Among compounds of the formula (I) useful in the practice of thisinvention, those represented by the following formula (Ia): ##STR13##wherein R¹ has the same meaning as defined above, R⁵¹ denotes analiphatic hydrocarbon group having 10-26 carbon atoms, and A' is a group--(--CH₂)_(l) OH (l: as defined above) or ##STR14## (X¹,X², X³ : asdefined above), with a proviso that X¹, X² and X³ do not mean H at thesame time, can be prepared, for example, in accordance with thefollowing reaction scheme. ##STR15##

Namely, the compound (Ia) is prepared by obtaining the compound (IIIa)from its corresponding glycidyl ether and amino-alcohol in accordancewith a process known per se in the art [Pol. J. Chem., 52, 1059(1978);ibid, 52, 1283(1978); Japanese Patent Laid-Open No. 117421/1979; ibid,144308/1979; ibid, 147937/1979] and then selectively acylating the aminogroup of the compound (IIIa) or acylating the compound (IIIa) and thenselectively hydrolyzing the ester moiety.

The reaction between the glycidyl ether and amino-alcohol may be carriedout by stirring the glycidyl ether and the amino-alcohol at 25°-150° C.for several tens minutes to 5 hours either without any solvent or in asolvent of a lower alcohol such as methanol, ethanol, propanol orisopropanol. Illustrative examples of the amino-alcohol may include3-amino-l-propanol, 4-amino-l-butanol, 5-amino-1-pentanol,6-amino-l-hexanol, 3-amino-l,2-propanediol,tris(hydroxymethyl)aminomethane, 1-amino-2-propanol, 2-amino-l-propanol,2-amino-l-butanol, 2-amino-1-pentanol, 2-amino-3-methyl-l-butanol,2-amino-1-hexanol, 2-amino-2-methyl-l-propanol,2-amino-2-methyl-1,3-propanediol and 2-amino-2-ethyl-1,3-propanediol.

The selective acylation of the amino group of the compound (IIIa) may beachieved, for example, by reacting the methyl ester of a long-chainfatty acid with the compound (IIIa) in the presence of a base, such asalkali hydroxide or alkali carbonate, under normal pressure or a reducedpressure up to 0.01 Torr at 25°-150° C. for several tens minutes to 5hours.

The non-selective acylation of the compound (IIIa) may be attained, forexample, by reacting a long-chain fatty acid halide with the compound(IIIa) in the presence of pyridine, a tertiary amine or the like. Theselective hydrolysis of the ester moiety of the resultant amide-esterderivative may be carried in a manner known per se in the art, using abase such as alkali hydroxide or alkali carbonate.

Of the compounds represented by the formula (I), those represented bythe following formula (Ib): ##STR16## wherein R¹ has the same meaning asdefined above, R⁵¹ denotes an aliphatic hydrocarbon group having 10-26carbon atoms, m' is an integer of at least 1, and n' stands for aninteger of at least 0, with a proviso that m' and n' do not mean 1 and 0respectively at the same time, may be prepared, for example, inaccordance with the following reaction scheme. ##STR17## Likewise thepreparation of the compound (IIIa), the compound (IIIb₁) or (IIIb₂) isobtained by reacting the corresponding glycidyl ether with theethanolamine or 2-aminoethoxyethanol. By adding ethylene oxide further,the compound (IIIb₃) is obtained. The compound (Ib) is then prepared byselectively acylating the amino group of the compound (IIIb₂) or (IIIb₃)or by non-selectively acylating the compound (IIIb₂) or (IIIb₃) and thenhydrolyzing the thus-acylated derivative in the same manner as in thepreparation of the compound (Ia).

Among the compounds represented by the formula (I), those represented bythe following formula (Ic): ##STR18## wherein R¹, R² and Y have the samemeaning as defined above, R⁵² denotes an aliphatic hydrocarbon grouphaving 8-26 carbon atoms, and W is 0 or CH₂, may be prepared, forexample, by a known process such as that disclosed in Japanese PatentLaid-Open No. 72118/1973 in accordance with the following reactionscheme. ##STR19## wherein Y' means an alkali metal or ester residuum.

Namely, the amido derivative (Ic) is prepared by reacting an alkalimetal salt or ester of an amino acid with the glycidyl ether or α-olefinepoxide derivative to form the compound (IIIc) and then acylating thecompound (IIIc).

As the amino acid, may be mentioned glycine, alanine, phenylalanine,valine, leucine, isoleucine, serine, methionine, aspartic acid, glutamicacid, histidine, tryptophan or the like. Its alkali metal salt may bethe lithium, sodium or potassium salt. Illustrative examples of itsester may include lower alkyl esters such as the methyl, ethyl,n-propyl, iso-propyl and butyl esters, the phenyl ester and the benzylester.

Among the compounds represented by the formula (I), those represented bythe following formula (Id): ##STR20## wherein R¹ has the same meaning asdefined above, and R⁵³ denotes an aliphatic hydrocarbon group having8-24 carbon atoms, may be prepared, for example, in accordance with thefollowing reaction scheme. ##STR21##

Namely, the compound (Id) is prepared by selectively acylating the aminogroup of the compound (IIId), which has been obtained by a reactionbetween an α-olefin epoxy compound and ethanolamine, or non-selectivelyacylating the compound (IIId) and then hydrolyzing the thus-acylatedderivative in the same manner as in the preparation of the compound(Ia).

Further, among the compounds (I), those represented by the followinggeneral formula (Ie): ##STR22## wherein R¹ have the same meaning asdefined above, R⁵¹ means an aliphatic hydrocarbon group having 10-26carbon atoms, and R³¹ and R³² denote individually H, sugar residuum orgroup ##STR23## (Z¹, Z², Z³ : as defined above), with a priviso that R³¹and R³² are not H at the same time and one of R³¹ and R³² is other thanthe sugar residuum when the other is the group ##STR24## may beprepared, for example, in accordance with the following reaction scheme.##STR25##

(1) Where R³¹ or R³² is a sugar residuum: ##STR26##

(2) Where R³¹ or R³² is a group ##STR27##

Namely, the compound (Ie) in Which R³ l or R³² is a sugar residuum isobtained by selectively acylating the amino group of the compound(IIIb₁) into the compound (IV) and then glycosylating the compound (IV).

The glycosylation of the compound (IV) may be effected by a method knownper se in the art, for example, by the Koenigs-Knorr synthesis, triflateprocess, trichloroacetimidate process, fluorinated glycoside process, orthe like. In the above glycosylation reaction, the glycosylationreaction is effected after protecting either one of the primary andsecondary hydroxyl groups with suitable protecting groups. Deprotectionof the protecting groups subsequent to the reaction affords a compoundof the formula (Ie) in which one of R³ l and R³² is a sugar residuum andthe other is a hydrogen atom. It is preferable to protect with suitableprotecting groups the hydroxyl groups of a sugar derivative to bereacted with the compound (IV).

As exemplary sugars corresponding to the sugar residua represented by R³l and R³² respectively in the formula (Ie), may be mentioned hexosessuch as glucose, galactose, mannose, fructose, sorbose, allose,2-deoxyglucose, 2-deoxygalactose and fucose; pentoses such as arabinose,lyxose, ribose, deoxyribose, ribulose, xylose and xylulose;disaccharides such as sucrose, cellobiose, lactose, maltose, melibiose,parathiose, trehalose and turanose; trisaccharides such as maltotriose;amino sugars such as glucosamine, galactosamine and mannosamine;N-acylated amino sugars such as N-acetylglucosamine,N-acetylgalactosamine and N-acetylmannosamine; glucocarboxylic acidssuch as glucuronic acid, galacturonic acid, N-acetylmuramic acid andN-acetylneuraminic acid; etc.

The followings are typical examples of glycosylation in the presentinvention.

(1) Reaction making use of DL-glucose: ##STR28##

(2) Reaction making use of DL-fucose: ##STR29##

(3) Reaction making use of DL-ribose: ##STR30##

(4) Reaction making use of lactose: ##STR31##

(5) Reaction making use of maltotriose: ##STR32##

(6) Reaction making use of glucosamine: ##STR33##

(7) Reaction making use of N-acetylneuraminic acid: ##STR34##

In the above formulae, the abbreviations have the following meaning: Et:ethyl, Me: methyl, Bn: benzyl, Ac: acetyl, Phth: phthaloyl, DMAP:N,N-dimethyl-aminopyridine.

Further, the compound (Ie) in which R³¹ or R³² ##STR35## may be preparedvia the dioxaphosphoran derivative (V) or oxaazaphosphoran derivative(VI) in accordance with a known process [N. T. Thuong, P. Chabrier,Bull. Soc. Chim. Fr., 1974, 667; N. S. Chandrakumar, J. Ha]du,Tetrahedron Lett., 22, 2949 (1981)].

The compounds of the formula (II) useful in the practice of thisinvention have already been known. Those represented by the formula (II)in which R⁸ is a group --CH₂ CH₂ OH or --COCH₃ can be prepared, forexample, by the process described in Polish. J. Chem., 52, 1059(1978)referred to above. On the other hand, the compound of the formula (II)in which R⁸ is a group --CH₂ COOH can be prepared, for example, inaccordance with the process of East German Patent No. 92940 (1973).

As illustrative examples of the salt of the compound (I) or (II) usefulin the practice of this invention, may be mentioned those usable incosmetic compositions, such as alkali metal salts.

No particular limitation is imposed on the proportion of the compoundrepresented by the formula (I) or (II) or a salt thereof in the externalskin care preparation. In the case of an emulsion-type external skincare preparation, its proportion may preferably be 0.001-50 wt. %(hereinafter indicated merely by "%"), notably, 0.1-20% of the wholepreparation. In the case of an oil-base external skin care preparationcontaining a liquid hydrocarbon such as squalene as a base, itsproportion may preferably be 1-50%, notably, 5-25%.

As a surfactant suitable for incorporation in the external skin carepreparation, any one of non-ionic surfactants, anionic surfactants andamphoteric surfactants may be mentioned. Of these, non-ionic surfactantsare especially suitable.

As exemplary non-ionic surfactants, may be mentioned polyoxyethylenealkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene fattyacid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fattyacid esters, fatty acid monoglycerides, glyceryl ethers, etc. Amongthese, glyceryl ethers represented by the following general formula(VII): ##STR36## wherein R means an alkyl group having 8-24 carbon atomsare preferred. Particularly preferred are glyceryl ethers of the formula(VII) in which R is represented by the following formula (VIII):##STR37## wherein p means an integer of 4-10, q denotes an integer of5-11, and p+q is 11-17 and is distributed with a peak at p=7 and q=8.

The proportion of the surfactant may be 0.01-20% of the wholepreparation, with 0.1-5% being particularly preferred.

External skin care preparations according to this invention may beclassified roughly into medicinal external skin care preparation andcosmetic preparations in accordance with their manner of use.

As exemplary medicinal external skin care preparations, may be mentionedvarious ointments containing one or more medicinally-effectiveingredients. Ointments include both those containing an oily base as abase and those containing an oil/water or water/oil emulsion-type baseas a base. No particular limitation is imposed on oily bases. Plantoils, animal oils, synthetic oils, fatty acids, natural and syntheticglycerides, etc. may be mentioned by way of example. No specificlimitation is imposed on medicinally-effective ingredients. For example,one or more of analgesic and antiphlogistic agents, antipruritics,disinfectants, astringents, emollients, hormones and the like may beused suitably as needed.

Where used as a cosmetic preparation, it is possible to mix in additionto the essential ingredients those employed routinely as cosmeticingredients such as oily substance, moisturizer, ultraviolet absorbent,alcohol, chelating agent, pH regulator, antiseptic, thickener, pigment,perfume base and the like in combination as needed.

As cosmetics, skin cosmetic preparations of various forms may beformulated including, for example, water/oil or oil/water typeemulsified cosmetics, creams, cosmetic emulsions, toilet waters, oilycosmetics, lip sticks, foundations, skin cleansing preparations, hairtonics, hair styling preparations, hair grooming preparations, hairgrowth stimulants, etc.

Having generally described the invention, a more complete understandingcan be obtained by reference to certain specific examples, which areprovided herein for purposes of illustration only and are not intendedto be limiting unless otherwise specified.

EXAMPLES

The present invention will hereinafter be described by the followingReferential Examples and Examples.

REFERENTIAL EXAMPLE 1 Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-3-hydroxypropylhexadecanamide (Ia₁)[in the formula (Ia), R¹ : C₁₅ H₃₁, A': --(--CH₂)₃ OH, R⁵¹ : C₁₆ H₃₃ ]

In a 200 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer, reflux condenser and nitrogen inlet tube25.0 g (0.333 mol) of 3-amino-1-propanol and 50 g of ethanol wereplaced. While stirring and heating the mixture at 80° C. in a nitrogenatmosphere, a solution of 10.0 g (0.034 mol) of hexadecyl glycidyl etherin 30 g of ethanol was added dropwise over 2 hours. After the additionwas completed, the heating and stirring were continued for additional 30minutes under the same conditions. A distillation apparatus wasconnected to the flask so as to distill off the ethanol and unreacted3-amino-1-propanol under reduced pressure, thereby obtaining 12.5 g of apale yellow solid. A 7.47 g (equivalent to 0.020 mol) portion of thecrude product was separated, to which 0.056 g of potassium hydroxide wasadded. While stirring the resultant mixture at 80° C./20 Torr, 5.42 g(0.020 mol) of methyl hexadecanoate was added dropwise over 1 hour.After the addition was completed, the mixture was stirred under heat for1 hour under the same conditions to obtain 12.2 g of a pale yellow crudeproduct. The crude product was recrystallized once from 120 g of hexaneand then once from 100 g of methanol, thereby obtaining 9.18 g of theintended compound (Ia₁) as colorless powder (overall yield: 75%).

Melting point: 82.4°-83.4° C.

IR (KBr, cm⁻¹): 3250, 2920, 2854, 1605, 1470, 1119.

¹ H-NMR (CDCl₃, δ): 0.87(6H,t), 1.1-2.0(56H,m), 2.42(2H,t),3.2-4.4(13H,m).

Elemental analysis: Calculated: C, 74.57%; H, 12.68%; N, 2.29%. Found:C, 74.67%; H, 12.73%; N, 2.21%.

REFERENTIAL EXAMPLE 2 Synthesis ofN-(3-hexadecylocy-2-hydroxypropyl)-N-6-hydroxyhexylhexadecanamide (Ia₂)[in the formula (Ia), R¹ : C₁₅ H₃₁, A': --(--CH₂)₆ OH, R⁵¹ : C₁₆ H₃₃ ]

In a 200 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer, reflux condenser and nitrogen inlet tube58.0 g (0.50 mol) of 6-amino-1-hexanol and 150 g of ethanol were placed.While stirring and heating the mixture at 80° C. in a nitrogenatmosphere, a solution of 15.0 g (0.050 mol) of hexadecyl glycidyl etherin 50 g of ethanol was added dropwise over 1 hour. After the additionwas completed, the heating and stirring were continued for additional 30minutes under the same conditions. A distillation apparatus wasconnected to the flask so as to distill off the ethanol and unreacted6-amino-1-hexanol under reduced pressure, thereby obtaining 15.8 g of apale yellow solid. A 8.3 g (equivalent to 0.020 mol) portion of thecrude product was separated, and was then dissolved in 200 ml ofmethylene chloride, followed by an addition of 4.8 g (0.06 mol) ofpyridine. Under water cooling, 16.5 g (0.06 mol) of hexadecanoylchloride was added dropwise over about 30 minutes. After the additionwas completed, the mixture was stirred at room temperature for 1 hour.The reaction mixture was washed with water to remove pyridiniumchloride, and the solvent was then distilled off to obtain 22.6 g of anamide-ester derivative.

Thereafter, the amide-ester derivative was dissolved in 400 g of 95%aqueous ethanol and 2.24 g (0.04 mol) of potassium hydroxide. Theresultant mixture was stirred at 50° C. for 1 hour. Chloroform-solubleportions were extracted from the reaction mixture and then purified byflash chromatography on a silica gel column, thereby obtaining 9.0 g(0.0138 mol) of the title compound as colorless powder (overall yield:52.4%).

Melting point: 78.8°-79.8° C.

IR (KBr, cm⁻¹): 3334, 2920, 2854, 1623, 1467, 1113.

¹ H-NMR (CDCl₃, δ): 0.87(6H,t), 1.2-1.9(62H,m), 2.41(2H,t),3.1-4.3(13H,m).

Elemental analysis: Calculated: C, 75.28%; H, 12.79%; N, 2.14%. Found:C, 75.33%; H, 12.83%; N, 2.09%.

REFERENTIAL EXAMPLE 3

Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2,3-dihydroxypropylhexadecanamide(Ia₃) [in the formula (Ia), R¹ : C₁₅ H₃₁, A': --CH₂ CH(OH)CH₂ OH, R⁵¹ :C₁₆ H₃₃ ]

In a 200 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer and reflux condenser were 48.3 g (0.50 mol)of 3-amino-1,2-propanediol and 150 g of ethanol. While stirring andheating the mixture at 80° C., a solution of 15.0 g (0.050 mol) ofhexadecyl glycidyl ether in 150 g of ethanol was added dropwise over 1hour. After the addition was completed, the heating and stirring werecontinued for additional 1 hour under the same conditions. The ethanoland unreacted 3-amino-1,2-propanediol were distilled off under reducedpressure, thereby obtaining 19.8 g of pale yellow solid.

Thereafter, the crude product was dissolved in 300 g of methylenechloride, followed by an addition of 15.8 g (0.20 mol) of pyridine.Under water-cooling, 54.8 g (0.20 mol) of hexadecanoyl chloride wasadded over about 30 minutes. After the addition was completed, thecontents were stirred at room temperature for 1 hour. The reactionmixture was then washed with water to remove pyridinium chloride, andthe solent was distilled off to obtain 64.0 g of an amide-esterderivative. The amide-ester derivative was thereafter dissolved in 500 gof 95% aqueous ethanol, to which was added 8.4 g (0.15 mol) of potassiumhydroxide. The mixture was stirred at 50° C. for 1 hour.Chloroform-soluble portions were extracted from the reaction mixture andthen purified by flash chromatography on a silica gel column, therebyobtaining 17.3 g (0.028 mol) of the title compound (Ia₃) as colorlesspowder.

Yield: 56%.

Melting point: 81.9°-83.3° C.

IR (KBr,cm⁻¹): 3370, 3292, 2920, 2854, 1608, 1470, 1113.

¹ H-NMR (CDCl₃, δ): 0.87(6H,t), 1.1-1.8(54H,m), 2.42(2H,t),3.2-4.4(15H,m).

Elemental analysis: Calculated: C, 72.67%; H, 12.36%; N, 2.23%. Found:C, 73.02%; H, 12.41%; N, 2.18%.

REFERENTIAL EXAMPLE 4 Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethoxyethylhexadecanamide(Ib₁) [in the formula (Ib), m': 2, n': 0, R¹ : C₁₅ H₃₁, R⁵¹ : C₁₆ H₃₃ ]

In a 200 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer and reflux condenser were 27.4 g (0.26 mol)of 2-aminoethoxy-ethanol and 100 g of ethanol were placed. Whilestirring and heating the mixture at 80° C., a solution of 15.0 g (0.050mol) of hexadecyl glycidyl ether in 50 g of ethanol was added dropwiseover 2 hours. After the addition was completed, the heating and stirringwere continued for additional 1 hour under the same conditions. Theethanol and unreacted 2-aminoethoxyethanol were distilled off underreduced pressure, thereby obtaining 17.7 g of an intermediate,N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylamine as pale yellowsolid.

Thereafter, the intermediate was dissolved in 300 g of methylenechloride, followed by an addition of 11.9 g (0.15 mol) of pyridine.Under water-cooling, 41.1 g (0.15 mol) of hexadecanoyl chloride wasadded over about 30 minutes. After the addition was completed, themixture was stirred at room temperature for 1 hour. The reaction mixturewas then washed with water to remove pyridinium chloride, and thesolvent was distilled off to obtain 53.8 g of an amide-ester derivative.The amide-ester derivative was thereafter dissolved in 400 g of 95%aqueous ethanol, to which 5.6 (0.10 mol) of potassium hydroxide wasadded. The mixture was stirred under heat at 40° C. for 30 minutes.

A chloroform-soluble fraction was extracted from the reaction mixtureand then purified by flash chromatography on a silica gel column,thereby obtaining 17.3 g (0.027 mol) of the title compound (Ib₁) ascolorless crystals.

Overall yield: 56% (based on the hexadecyl glycidyl ether).

Melting point: 68.0-69.3° C.

IR (KBr,cm⁻¹): 3406, 2920, 2854, 1647, 1473, 1119.

¹ H-NMR (CDCl₃, δ): 0.87(6H,t), 1.1-1.8(54H,m), 2.40(2H,t),3.3-4.4(17H,m).

Elemental analysis: Calculated: C, 72.96%; H, 12.40%; N, 2.18%. Found:C, 73.17%; H, 12.44%; N, 2.16%.

REFERENTIAL EXAMPLE 5 Synthesis ofN-(2-hydroxyethyl)-N-2-hydroxyhexadecyloctadecanamide (Id₁) [in theformula (Id), R¹ : C₁₇ H₃₅, R⁵³ : C₁₄ H₂₉ ]

In a 500 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer, reflux condenser and nitrogen inlet tube,117 g (1.91 mol) of monoethanolamine and 117 g of ethanol were placed.While stirring and heating the mixture at 80° C. in a nitrogenatmosphere, a solution of 26.8 g (0.10 mol) of 1,2-epoxyoctadecane in53.6 g of ethanol was added dropwise over 90 minutes. After the additionwas completed, the heating and stirring were continued for additional 1hour under the same conditions. A distillation apparatus wa connected tothe flask so as to distill off the ethanol and unreacted ethanolamineunder reduced pressure. The residue was recrystallized from 250 ml ofmethanol, thereby obtaining 24.0 g of a long-chain ethanolamineintermediate as a pale yellow solid.

A 20.0 g (0.060 mol) portion of the crude product was separated, towhich 0.225 g of potassium hydroxide was added. While stirring theresultant mixture at 80° C./20 Torr, 18.0 g (0.060 mol) of methyloctadecanoate was added dropwise over 1 hour. After the addition wascompleted, the mixture was stirred under heat for 1 hour under the sameconditions to obtain a crude product as pale yellow solid. It was thenpurified by flash chromatography on a silica gel column, therebyobtaining 18.5 g (0.031 mol) of the title compound (Id₁) as colorlesscrystals.

Overall yield: 62.0% (based on the 1,2-epoxyoctadecane).

Melting point: 72.3°-73.8° C.

IR (KBr, cm⁻¹): 3436, 2920, 2854, 1602, 1473, 1080.

¹ H-NMR (CDCl₃, δ): 0.87(6H,t), 1.1-1.7(60H,m), 2.37(2H,t),3.1-4.1(9H,m).

Elemental analysis: Calculated: C, 76.58%; H, 13.02%; N, 2.35%. Found:C, 76.78%; H, 13.05%; N, 2.28%.

REFERENTIAL EXAMPLE 6 Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-(2-O-glucopyranosyl)ethylhexadecanamide(Ie₁) [in the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ : glucopyranosyl, R³² H,R⁵¹ : C₁₆ H₃₃ ] a) Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide (IVa)[in the formula (IV), R¹ : C₁₅ H₃₁, R⁵¹ : C₁₆ H₃₃ ]

In a 5 l four-necked flask equipped with a mechanical stirrer, droppingfunnel, thermometer, reflux condenser and nitrogen inlet tube, 1637 g(26.8 mol) of ethanolamine and 327 g (7.11 mol) of ethanol were placed.While stirring and heating the mixture at 80° C. in a nitrogenatmosphere, 400 g (1.34 mol) of hexadecyl glycidyl ether was addeddropwise over 3 hours. After the addition was completed, the heating andstirring were continued for additional 30 minutes under the sameconditions. A distillation apparatus was connected to the flask so as todistill off the ethanol and unreacted ethanolamine under reducedpressure (79°-81° C./20 Torr). A crude product was added with 3.76 g(0.067 mol) of potassium hydroxide. While stirring the resultant mixtureat 80° C./20 Torr, 362.3 g (1.34 mol) of methyl hexadecanoate was addeddropwise over 3 hours. After the addition was completed, the mixture wastirred under heat for 1 hour under the same conditions to obtain 801 gof a crude product as a pale yellow solid. The crude product wasrecrystallized once from hexane and then twice from ethanol, therebyobtaining 649 g of the title compound (IVa) as colorless powder (yield:81%).

Melting point: 74°-76° C.

IR (KBr,cm⁻¹): 3320(br.), 2924, 2852, 1616, 1468, 1112, 1062.

¹ H-NMR (CDCl₃, δ): 0.86(6H,t), 1.0-1.6(54H,m), 2.2-2.5(2H,m),3.2-4.1(13H,m).

Elemental analysis: Calculated: C, 74.31%; H, 12.64%; N, 2.34%. Found:C, 74.12%; H, 12.70%; N, 2.23%.

b) Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2-triphenylmethoxyethylhexadecanamide

In a 500 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, thermometer, reflux condenser and nitrogen inlet tube,59.81 g (0.1 mol) ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethylhexadecanamide (IVa)obtained in the step a), 28.73 g (0.101 mol) of triphenylmethyl chlorideand 300 ml of dry dichloromethane were stirred under nitrogen. Asolution of 8.70 g (0.11 mol) of pyridine in 50 ml of drydichloromethane was added dropwise to the above-prepared mixture overabout 5 minutes, followed by heating under reflux at 40° C. for 6 hours.After the reaction was completed, the reaction mixture was cooled down,and precipitated pyridinium chloride was filtered off. The filtrate waswashed four times with 100 ml of water and then dried over anhydroussodium sulfate. The solvent was distilled off to obtain 77.11 g of acrude product as a colorless wax. The crude product was purified byflash chromatography on a silica gel column (silica gel: 230-400 mesh, 1kg; solvent: dichloromethane/ethyl acetate=19/1), thereby obtaining59.37 g of the title compound as colorless wax (yield: 70.7%).

Melting point: 46°-47° C.

IR (KBr,cm⁻¹): 3412, 3058, 3028, 2926, 2854, 1653, 1626, 1473, 1452,1083, 705.

¹ H-NMR (CDCl₃, δ): 1.86(6H,t), 1.0-1.6(54H,m), 2.2-2.5(2H,m),3.2-4.1(12H,m), 7.2-7.5(15H,m).

c) Synthesis(2-benzyloxy-3-hexadecyloxy-propyl)-N-2-hydroxyethylhexadecanamide

In a 200 ml four-necked flask equipped with a stirrer, dropping funnel,thermometer, reflux condenser and nitrogen inlet tube, 58.82 g (0.07mol) of N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-triphenylmethoxyethylhexadecanamide obtained in the step b) was dissolved by 100 ml ofN,N-dimethylformamide under nitrogen. The resultant solution was thenadded with 5.6 g (0.14 mol) of sodium hydride (as 60% solution in amineral oil), followed by stirring at room temperature for 3 hours.After foaming had ceased, the mixture was heated to 60° C. and 17.90 g(0.14 mol) of benzyl chloride was added over 20 minutes. Aftercompletion of the dropwise addition, the mixture was stirred at 60° C.for 1.5 hours. After completion of the reaction, water was addeddropwise under nitrogen to decompose excess sodium hydride. The reactionmixture was then poured into 500 ml of water. The resultant mixture wasextracted with hexane. The hexane layer was washed twice with water andonce with saturated aqueous sodium chloride, and was dried overanhydrous sodium sulfate. The solvent was distilled off to obtain 72.8 gof a crude product as a pale yellow oil. The crude product was purifiedby flash chromatography on a silica gel column (silica gel: 230-400mesh, 1 kg; solvent: hexane/ethyl acetate=9/1), thereby obtaining 59.5 gofN-(2-benzyloxy-3-hexadecyloxypropyl)-N-2-triphenylmethoxyethylhexadecanamideas a pale yellow oily wax.

Under nitrogen, 55.83 g (0.06 mol) of the above compound, 6 ml (0.072mol) of concentrated hydrochloric acid and 100 ml of dioxane werestirred at room temperature for 9 hours. After completion of thereaction, the dioxane was distilled off, 100 ml of dichloromethane wasadded, and the mixture was then neutralized with aqueous sodiumbicarbonate. Subsequent to the collection of a dichloromethane layer,the dichloromethane solution was washed with saturated aqueous sodiumchloride and then dried over anhydrous sodium sulfate. The solvent wasthereafter distilled off to obtain 58.02 g of a crude product as a paleyellow oil. The crude product was purified by flash chromatography on asilica gel column and further by medium-pressure liquid chromatography,thereby obtaining 14.17 g of the title compound as a colorless wax(yield: 31.4%).

Melting point: 39°-40° C.

IR (KBr,cm⁻¹): 3412, 2920, 2854, 1647, 1626, 1473, 1116, 1089, 1032.

¹ H-NMR (CDCl₃, δ): 0.86(6H,t), 1.1-1.5(54H,br.s), 2.26(2H,m),3.3-3.8(12H,m), 4.51(1H, d,J=12.0Hz), 4.64(1H,dd,J=12.0, 1.6Hz),7.31(5H,br.s).

d) Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-(2-O-glucopyranosyl)ethylhexadecanamide(Ie₁) [In the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ : glucopyranosyl, R³² : H,R⁵¹ : C₁₆ H₃₃ ]

In a 100-ml round bottom flask equipped with a mechanical stirrer,calcium chloride tube and dropping funnel, 1.08 g (1.57 mmol) ofN-(2-benzyloxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamideobtained in the above step c) and 1.40 g (2.04 mmol) ofO-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl) trichloroacetoimidateprepared by a known process [Liebig's Annalen der Chemie, 1249(1983)]were dissolved in 10 ml of dry dichloromethane. The reaction mixture wasthen stirred at room temperature. A solution of 0.29 g (2.04 mmol) ofboron trifluoride diethyl etherate in 1 ml of dry dichloromethane wasadded to the mixture over 5 minutes. The resultant mixture was stirredat room temperature for 1 hour. After completion of the reaction, thereaction mixture was neutralized with a saturated aqueous sodiumbicarbonate and then added with 40 ml of dichloromethane. Thedichloromethane layer was washed with saturated aqueous sodium chlorideand then dried over anhydrous sodium sulfate. The solvent was thereafterdistilled off to obtain 2.215 g of a crude product as a pale yellow oil.The crude product was purified by medium-pressure liquid chromatographyto obtain 1.514 g of a pentabenzylglycoside derivative as a colorlessoil. In a mixed solvent of 100 ml of ethanol and 50 ml of methanol 1.21g (1.0 mmol) of the thus-obtained pentabenzylglycoside derivative and1.0 g of palladium black were suspended. In an 200 ml autoclave, thepentabenzylglycoside derivative was subjected to hydrogenation at24°-28° C. for 7 hours under a hydrogen pressure of 112-127 Kg/cm².Chloroform was added to the reaction mixture to dissolve a white solidsuspended therein. After separation of the palladium black byfiltration, the solvent was distilled off to obtain 0.6 g of anamorphous crude product as a pale yellow solid. The crude product waspurified by medium-pressure liquid chromatography (silica gel: 25-40 μm,75 g; developer: chloroform/methanol=50/1), thereby obtaining 0.537 g ofthe title compound (Ie₁) as a colorless amorphous solid (yield: 56.5%).The thus-obtained compound was a mixture of the α-glucopyranosyl andβ-glucopyranosyl derivative at a ratio of about 1:9. ##STR38##

Melting point: 153°-154° C.

IR (KBr,cm⁻¹): 3416, 2920, 2852, 1626, 1470, 1106, 1080, 1038.

¹ H-NMR (CDCl₃, δ): 0.86(6H,t), 1.1-1.7(60H,br.s), 2.2-6.0(25H,br.s).

Elemental analysis: Calculated: C, 67.94%; H, 11.27%; N, 1.84%. Found:C, 67.68%; H, 11.30%; N, 1.82%.

REFERENTIAL EXAMPLE 7 Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-[2-O-(4-O-β-D-galactopyranosyl-.beta.-D-glucopyranosyl)ethyl]hexadecanamide(Ie₂) [in the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :4-O-β-D-galactopyranosyl-β-D-glucopyranosyl, R³² : H, R⁵¹ : C₁₆ H₃₃ ] a)Synthesis ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide

In a 30 ml four-necked flask equipped with a magnetic stirrer, droppingfunnel, thermometer, reflux condenser and nitrogen inlet tube, 500 mg(0.595 mmol) ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-2-triphenylmethoxyhexadecanamideobtained in the step b) of Referential Example 6 was dissolved in 10 mlof dry dichloromethane. To the resultant solution, 4 ml of pyridine and2 ml of acetic anhydride were successively added dropwise over 30minutes. The mixture was stirred for 8 hours at room temperature. Aftercompletion of the reaction, the reaction mixture was washed first with2N hydrochloric acid and then with water. The reaction mixture was driedover salt cake and the solvent was then distilled off. The residue waspurified by preparative thin-layer chromatography on silica gel, therebyobtaining 520 mg ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-2-triphenylmethoxyethylhexadecanamide.In a 10-ml two-necked flask, a 105 mg (0.119 mmol) portion of thecompound was dissolved in 2 ml of dry dichloromethane, followed by anaddition of 0.6 ml (0.505 mmol) of a 17% hexane solution ofdiethylaluminum chloride. After stirring the mixture for 40 minutes, a5% aqueous sodium bicarbonate was added to terminate the reaction. Awhite insoluble matter thus formed was collected by filtration throughCelite (trade mark), washed with water and then dried over salt cake.The solvent was distilled off. The residue was then purified bypreparative thin-layer chromatography on silica gel to obtain 73 mg ofthe intended compound as colorless crystals (yield: 95%).

Melting point: 59.5°-60.0° C.

IR (KBr, cm⁻¹): 3514, 2920, 2854, 1713, 1641, 1473, 1386, 1275, 1224,1206, 1146, 1077, 1050.

¹ H-NMR (CDCl₃, δ): 0.88(6H,t), 1.2-1.8(54H,m), 2.07(3H,s), 2.38(2H,m),3.3-3.9(11H,m), 5.1-5.3(1H,m).

b) Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-[2-O-(4-O-β-D-galactopyranosyl-.beta.-D-glucopyranosyl)ethyl]hexadecanamide(Ie₂) [In the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :4-O-β-D-galactopyranosyl-β-D-glucopyranosyl, R³² : H, R⁵¹ : C₁₆ H₃₃ ]

In a 100 ml four-necked flask equipped with a mechanical stirrer, sealumcap, reflux condenser, thermometer and nitrogen inlet tube, 5.19 g (8.11mmol) of N-(2-acetoxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamide obtained in the above step a) and 5.5 g (8.11 mmol) ofβ-D-lactose octaacetate prepared by a known process [Journal of AmericanChemical Society, 47, 2052(1925)] were dissolved in 20 ml of drydichloromethane, followed by an addition of 2.0 g of powdery molecularsieves 4A. The mixture was stirred at room temperature for 30 minutesunder a nitrogen, to which 2.14 g (9.63 mmol) of trimethylsilyl triflatewas added by a syringe. After stirring the resultant mixture for further6 hours under the above conditions, the resultant suspension wasfiltered. The filtrate was washed first with a 5% aqueous sodiumbicarbonate and then with water, and was thereafter dried over anhydroussodium sulfate. The solvent was distilled off to obtain a crude productas a pale yellow oil. After dissolving the crude product in 50 ml ofmethanol, 14.1 g (73 mmol) of a 28% methanol solution of sodiummethoxide was added dropwise at room temperature. The mixture was thenstirred for 3 hours. "Amberlyst 15" (trade name) was added to thereaction mixture to neutralize same. The "Amberlyst" was filtered offand the filtrate was concentrated to dryness. The resultant crudeproduct as a pale yellow solid was purified by chromatography on asilica gel column (silica gel: 230-400 mesh, 300 g; solvent:chloroform/methanol=4/1), thereby obtaining 2.50 g of the title compound(Ie₂) as colorless powder (yield: 31.4%). ##STR39##

Melting point: 235° C. (decomposed).

IR (KBr, cm⁻¹): 3484, 3412, 1641, 1119, 1104, 1074, 1056, 1035.

¹ H-NMR (DMSO--d₆ /D₂ O=9/1,50° C., δ): 0.849(6H,t,J=6.96Hz),1.237(50H,s), 1.482(4H,br.s), 2.290(2H,m), 3.03-3.77 (22H,m),4.19-4.97(3H,m).

Elemental analysis: Calculated: C, 63.81%; H, 10.38%; N, 1.52%. Found:C, 63.61%; H, 10.43%; N, 1.50%.

REFERENTIAL EXAMPLE 8 Synthesis ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-[2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)ethyl]hexadecanamide(Ie₃) [in the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :2-acetamido-2-deoxy-β-D-glucopyranosyl, R³² : H, R⁵¹ : C₁₆ H₃₃ ] a)Synthesis ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-[2-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)ethyl]hexadecanamide

In a 200 ml four-necked flask equipped with a mechanical stirrer, refluxcondenser, thermometer and nitrogen inlet tube, 5.0 g (7.81 mmol) ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-2-hydroxyethylhexadecanamideobtained in the step a) of Referential Example 7 and 7.0 g (21.3 mmol)of2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazolineprepared by a known process [Carbohydrate Research, 103, 286 (1982)]weredissolved in 120 ml of dry 1,2-dichloroethane. To the resultantsolution, 1.3 g (5.17 mmol) of pyridinium p-toluenesulfonate was added.The mixture was heated under reflux for 24 hours. The reaction mixturewas washed successively with a 5% aqueous sodium bicarbonate and waterand was then dried over anhydrous sodium sulfate. The solvent wasdistilled off to obtain a crude product as a pale yellow oil. The crudeproduct was purified by chromatography on a silica gel column (silicagel: 230-400 mesh, 600 g; solvent: ethyl acetate/hexane=4/1), therebyobtaining 4.93 g of the title compound as a colorless oil (yield:69.8%). ##STR40##

IR (liquid film, cm⁻¹): 3296, 1746, 1658, 1236, 1048.

¹ H-NMR (CDCl₃, δ): 0.880(6H,t,J=2.93Hz), 1.256(50H,s), 1.566(4H,m),1.923,l.932(3H,s,NHAc), 2.021(9H,s,OAc), 2.054,2061(3H,s,OAc),2.086,2.091(3H,s,OAc), 3.405-4.29(l3H,m), 4.590,4.625,4.649,4.744(1H,each d,J=8.43Hz,1'-H), 5.024-5.251(3H,m,--CHOAc), 5.854, 5.918,5.952,5.986(1H,each d,J=8.43Hz, ##STR41##

Elemental analysis: Calculated: C, 65.67%; H, 9.98%; N, 2.89%. Found: C,65.56%; H, 9.91%; N, 2.76%.

b) Synthesis ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-[2O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)ethyl]hexadecanamide(Ie₃) [In the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :2-acetamido-2-deoxy-β-D-glucopyranosyl, R³² : H, R⁵¹ : C₁₆ H₃₃ ]

In a 100 ml four-necked flask equipped with a magnetic stirrer, droppingfunnel, reflux condenser, thermometer and nitrogen inlet tube, 4.30 g(4.44 mmol) ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-[2-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)ethyl]hexadecanamideobtained in the above step a) was dissolved in 30 ml of drydichloromethane, followed by a dropwise addition of 3.67 g (19.03 mmol)of a 28% methanol solution of sodium methoxide at room temperature undernitrogen. The mixture was stirred for 1 hour as was. After neutralizingthe reaction mixture with 10 g of "Amberlyst 15", the "Amberlyst"wasfiltered off and the filtrate was concentrated. The residue was purifiedby column chromatography on a silica gel column (silica gel: 230-400mesh, 150 g; solvent: chloroform/methanol=10/1), followed byrecrystallization from a chloroform/acetone to obtain 2.45 g of thetitle compound (Ie₃) as colorless powder (yield: 68.6%). ##STR42##

Melting point: 146.8°-148.8° C.

IR (KBr, cm⁻¹) 3428, 1624, 1112, 1080.

¹ H-NMR (DMSO-d₆, δ): 0.854(6H,t), 1.237(50H,s), 1.470(4H,m),1.798(3H,d,J=5.12Hz,--NHAc), 2.27(2H,m), 3.08-3.85(18H,m),4.21-4.95(5H,m).

Elemental analysis: Calculated: C, 67.46%; H, 11.07%; N, 3.50%. Found:C, 67.08%; H, 11.00%; N, 3.31%.

REFERENTIAL EXAMPLE 9 Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-[2-O-(5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosyl)ethyl]hexadecanamide(Ie₄) [in the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosyl, R³² :H, R⁵¹ : C₁₆ H₃₃ ] a) Synthesis ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-[2-O-(methyl5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosonate)ethyl]hexadecanamide

In a 50-ml four-necked flask, 2.86 g (4.48 mmol) ofN-(2-acetoxy-3-hexadecyloxypropyl)-N-2-hydroxyethyl hexadecanamideprepared in the step a) of Referential Example 7 and 1.90 g (3.73 mmol)of methyl 2-deoxy-2-chloro-4,7,8,9-tetra-O-acetyl-N-acetylneuramin ateprepared by a known process [Chemische Berichte, 99, 611(1966); Chemicaland Pharmaceutical Bulletin, 34, 2725(1986)] were dissolved in a mixedsolvent of 5.0 ml of dry dichloromethane and 5.0 ml of dry toluene. Atroom temperature and under a nitrogen, 2.0 g of anhydrous calciumsulfate powder was added and the resultant mixture was stirred for 30minutes. 1.54 g (5.60 mmol) of silver carbonate powder was added to thereaction mixture. After stirring the mixture at room temperature forfurther 3.5 hours, an insoluble matter was filtered off. The filtratewas concentrated under reduced pressure, and then purified bychromatography on a silica gel column (silica gel: 230-400 mesh, 300 g;solvent: ethyl acetate/hexane=3/1), thereby obtaining 3.06 g of thetitle compound as a colorless oil (yield: 73.7%). ##STR43##

IR (liquid film, cm⁻¹): 3220, 1749, 1662, 1224, 1131, 1044.

¹ H-NMR (CDCl₃, δ): 0.879(6H,t,J=6.59Hz), l.257(50H,s), 1.569(4H,m),1.881(3H,s,HNAc), 2.025, 2.040,2.049,2.060,2.121,2.139,2.156 (15H, eachs,OAc), 2.34(2H,m),2.564 (1H,dd,J=5.1and 13.7Hz,3'-Heq),3.409-4.16(13H,m), 3.778(3H,s,COOMe), 4.259(1H,m,9'-H),4.86(1H,m,CHOAc), 5.08-5.41(4H,m,4'-H,7'-H,8'-H,NH Ac).

Elemental analysis: Calculated: C, 63.64%; H,9.41%; N, 2.52%. Found: C,63.58%; H, 9.41% N, 2.34%.

b) Synthesis ofN-(3-hexadecyloxy-2-hydroxypropyl)-N-[2-O-(5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosyl)ethyl]hexadecanamide(Ie₄) [In the formula (Ie), R¹ : C₁₅ H₃₁, R³¹ :5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosyl, R³² :H, R⁵¹ : C₁₆ H₃₃ ]

In a 200 ml four-necked flask equipped with a mechanical stirrer,dropping funnel, reflux condenser, thermometer and nitrogen inlet tube,2.10 g (1.89 mmol) of N-(2-acetoxy-3-hexadecyloxypropyl)-N-[2-O-(methyl5-acetamido-3,5-dideoxy-α-D-glycero-β-D-galacto-2-nonuropyranosonate)ethyl]hexadecanamideprepared in the above step a) was dissolved in 30 ml of dry pyridine,followed by an addition of 1.50 g (11.2 mmol) of lithium iodide. Undernitrogen, the reaction mixture was stirred for 4 hours under heat.Chloroform was added to the reaction mixture. The resultant mixture waswashed successively with 2N hydrochloric acid and water, followed byseparation of a chloroform solution. The chloroform solution was thendried over anhydrous sodium sulfate. The solvent was distilled off toobtain a pale-yellow oil. The crude oil was dissolved in 100 ml of drydichloromethane, to which 2.2 g (11.4 mmol) of a 28% methanol solutionof sodium methoxide was added dropwise at room temperature undernitrogen. The mixture was stirred for 3 hours. The reaction mixture wasthereafter stirred for 3 hours together with 10 g of "Amberlyst 15" soas to neutralize same, and a solid matter was filtered off. The filtratewas concentrated and then purified by column chromatography on a silicagel column (silica gel: 230-400 mesh, 150 g; solvent:chloroform/methanol/water=100/40/1), thereby obtaining 1.209 g of thetitle compound (Ie₄) as colorless powder (yield: 75.7%). ##STR44##

Melting point: 202° C. (decomposed).

IR (KBr, cm⁻¹): 3388, 1620, 1122, 1077, 1032.

¹ H-NMR (DMSO-d₆ /D₂ O=100/1, 35° C., δ): 0.816(6H,br.s),1.212(50H,br.s), 1.46(4H,br.s), 1.808, 1.922(3H,each s,NHAc),2.30(2H,m), 2.69(1H,m,3eq-H), 3.23-3.83(18H,m).

Elemental analysis: Calculated: C, 64.83%; H, 10.43%; N, 3.15%. Found:C, 64.83%; H, 10.50%; N, 3.02%.

EXAMPLE 1

Compounds Ia₁ -Ia₁₈ prepared respectively in Referential Examples 1, 2and 3 and following the procedures of these referential examples,compounds Ib₁ -Ib₅ prepared respectively in Referential Example 4 andfollowing the procedure of the referential example, compounds Id₁ -Id₅prepared respectively in Referential Example 5 and following theprocedure of the referential example, compounds Ie₁ -Ie₄ preparedrespectively in Referential Examples 6-9, and conventional compounds Ic₁-Ic₁₃, Ie₅ -Ie₁₄ and II₁ -II₁₂ were used separately. Mixtures (InventionProducts 1), each of which had been formulated by mixing vaseline andthe compound (I or II) at a weight ratio of 3:1, and vaseline(Comparative Product 1) were evaluated in skin conductance and skinroughness by the following methods. Results will be summarized in Table1.

TESTING METHODS

Chosen as volunteers in winter were 10 women of 20-50 years of old whohad skin roughness on their both cheeks. Different external skin carepreparations were coated separately o the left and right cheeks of eachvolunteer for two weeks. On the following day of the the completion ofthe two-week coating test, tests were conducted with respect to thefollowing properties.

(1) SKIN CONDUCTANCE

After washing the face with warm water of 37° C., each volunteer wasallowed to rest for 20 minutes in a room which was air-conditioned at20° C. and 40% humidity. The water content of her horny layer wasmeasured by a skin conductance meter (manufactured by IBS Company). Asmaller conductance value indicates greater skin roughness. Conductancevalues of 5 and smaller indicate severe skin roughness. On the contrary,no substantial skin roughness is observed where this value is 20 orgreater.

(2) SCORE OF SKIN ROUGHNESS

Skin roughness was observed visually and ranked in accordance with thefollowing standard. Each score was indicated by an average value.

    ______________________________________                                        Score     Ranking of skin roughness                                           ______________________________________                                        0         No skin roughness was observed.                                     1         Slight skin roughness was observed.                                 2         Skin roughness was observed.                                        3         Rather severe skin roughness was observed.                          4         Severe skin roughness was observed.                                 ______________________________________                                    

                                      TABLE 1-1                                   __________________________________________________________________________                                        Skin Score of                             Compound    Formula (Ia)            conduc-                                                                            skin                                 No.         R.sup.1                                                                            R.sup.51                                                                           A'            tance                                                                              roughness                            __________________________________________________________________________    Invention                                                                           Ia.sub.1                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                --(CH.sub.2).sub.3 OH                                                                       20   1.1                                  Product 1                                                                           Ia.sub.2                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                --(CH.sub.2).sub.6 OH                                                                       18   1.3                                        Ia.sub.3                                                                            n-C.sub.9 H.sub.19                                                                 n-C.sub.10 H.sub.21                                                                --(CH.sub.2).sub.3 OH                                                                       10   1.5                                        Ia.sub.4                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.10 H.sub.21                                                                --(CH.sub.2).sub.3 OH                                                                       13   1.4                                        Ia.sub.5                                                                            n-C.sub.9 H.sub.19                                                                 n-C.sub.18 H.sub.37                                                                --(CH.sub.2).sub.3 OH                                                                       17   1.2                                        Ia.sub.6                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --(CH.sub.2).sub.3 OH                                                                       23   0.9                                        Ia.sub.7                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.10 H.sub.21                                                                --(CH.sub.2).sub.6 OH                                                                       11   1.5                                        Ia.sub.8                                                                            n-C.sub.10 H.sub.21                                                                n-C.sub.18 H.sub.37                                                                --(CH.sub.2).sub.6 OH                                                                       13   1.4                                        Ia.sub.9                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --(CH.sub.2).sub.6 OH                                                                       20   1.1                                        Ia.sub.10                                                                           n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                --CH.sub.2 CH(OH)CH.sub.2 OH                                                                22   0.9                                        Ia.sub.11                                                                           n-C.sub.17 H.sub.35                                                                n-C.sub.10 H.sub.21                                                                --CH.sub.2 CH(OH)CH.sub.2 OH                                                                19   1.0                                        Ia.sub.12                                                                           n-C.sub.9 H.sub.19                                                                 n-C.sub.18 H.sub.37                                                                --CH.sub.2 CH(OH)CH.sub.2 OH                                                                18   1.1                                        Ia.sub.13                                                                           n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --CH.sub.2 CH(OH)CH.sub.3                                                                   13   1.3                                        Ia.sub.14                                                                           n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --C(CH.sub.3)(CH.sub.2 OH)CH.sub.2 OH                                                       23   0.8                                        Ia.sub.15                                                                           n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --C(CH.sub.3).sub.2 CH.sub.2 OH                                                             13   1.3                                        Ia.sub.16                                                                           n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                --CH(CH.sub.3)CH.sub.2 OH                                                                   15   1.2                                        Ia.sub.17                                                                           n-C.sub.9 H.sub.19                                                                 n-C.sub.14 H.sub.29                                                                --C(CH.sub.2 OH).sub.3                                                                      20   1.0                                  __________________________________________________________________________

                                      TABLE 1-2                                   __________________________________________________________________________                                Skin Score of                                     Compound    Formula (Ib)    conduc-                                                                            skin                                         No.         R.sup.1                                                                            R.sup.51                                                                           m' n' tance                                                                              roughness                                    __________________________________________________________________________    Invention                                                                           Ib.sub.1                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                2  0  20   1.0                                          Product 1                                                                           Ib.sub.2                                                                            n-C.sub.9 H.sub.19                                                                 n-C.sub.10 H.sub.21                                                                2  0  10   1.6                                                Ib.sub.3                                                                            n-C.sub.9 H.sub.19                                                                 n-C.sub.18 H.sub.37                                                                2  0  14   1.5                                                Ib.sub.4                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.10 H.sub.21                                                                2  0  17   1.2                                                Ib.sub.5                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.18 H.sub.37                                                                2  0  23   0.9                                          __________________________________________________________________________

                                      TABLE 1-3                                   __________________________________________________________________________                                       Skin Score of                              Compound                                                                            Formula (Ic)                 conduc-                                                                            skin                                  No.   R.sup.1                                                                            R.sup.2       R.sup.52                                                                           Y W  tance                                                                              roughness                             __________________________________________________________________________    Invention Product 1                                                           Ic.sub.1                                                                            n-C.sub.17 H.sub.35                                                                H             n-C.sub.14 H.sub.29                                                                H O  14   1.5                                   Ic.sub.2                                                                            n-C.sub.17 H.sub.35                                                                H             n-C.sub.14 H.sub.29                                                                Na                                                                              O  15   1.4                                   Ic.sub.3                                                                            n-C.sub.17 H.sub.35                                                                H             n-C.sub.14 H.sub.29                                                                H CH.sub.2                                                                         11   1.7                                   Ic.sub.4                                                                            n-C.sub.17 H.sub.35                                                                H             n-C.sub.14 H.sub.29                                                                Na                                                                              CH.sub.2                                                                         13   1.4                                   Ic.sub.5                                                                            n-C.sub.15 H.sub.31                                                                CH.sub.3      n-C.sub.16 H.sub.33                                                                K O  13   1.4                                   Ic.sub.6                                                                            n-C.sub.15 H.sub.31                                                                PhCH.sub.2    n-C.sub.16 H.sub.33                                                                K O  12   1.6                                   Ic.sub.7                                                                            n-C.sub.15 H.sub.31                                                                (CH.sub.3).sub.2 CH                                                                         n-C.sub.16 H.sub.33                                                                K O  15   1.4                                   Ic.sub.8                                                                            n-C.sub.15 H.sub.31                                                                HOCH.sub.2    n-C.sub.16 H.sub.33                                                                K O  18   1.2                                   Ic.sub.9                                                                            n-C.sub.15 H.sub.31                                                                CH.sub.3 SCH.sub.2 CH.sub.2                                                                 n-C.sub.16 H.sub.33                                                                K O  16   1.3                                    Ic.sub.10                                                                          n-C.sub.15 H.sub.31                                                                YOCOCH.sub.2  n-C.sub.16 H.sub.33                                                                H O  15   1.4                                    Ic.sub.11                                                                          n-C.sub.15 H.sub.31                                                                YOCOCH.sub.2 CH.sub.2                                                                       n-C.sub.16 H.sub.33                                                                H O  13   1.5                                    Ic.sub.12                                                                          n-C.sub.15 H.sub.31                                                                 ##STR45##    n-C.sub.16 H.sub.33                                                                K O  11   1.8                                    Ic.sub.13                                                                          n-C.sub.15 H.sub.31                                                                 ##STR46##    n-C.sub.16 H.sub.33                                                                K O  10   1.9                                   __________________________________________________________________________

                                      TABLE 1-4                                   __________________________________________________________________________                              Skin  Score of                                      Compound     Formula (Id) conduc-                                                                             skin                                          No.          R.sup.1                                                                              R.sup.53                                                                            tance roughness                                     __________________________________________________________________________    Invention                                                                           Id.sub.1                                                                             n-C.sub.17 H.sub.35                                                                  n-C.sub.14 H.sub.29                                                                 21    1.0                                           Product 1                                                                           Id.sub.2                                                                             n-C.sub.9 H.sub.19                                                                   n-C.sub.16 H.sub.33                                                                 18    1.1                                                 Id.sub.3                                                                             n-C.sub.9 H.sub.19                                                                   n-C.sub.10 H.sub.21                                                                 13    1.3                                                 Id.sub.4                                                                             n-C.sub.17 H.sub.35                                                                  n-C.sub.10 H.sub.21                                                                 17    1.1                                                 Id.sub.5                                                                             cis-9-C.sub.17 H.sub.33                                                              n-C.sub.16 H.sub.33                                                                 25    0.8                                           __________________________________________________________________________

                                      TABLE 1-5                                   __________________________________________________________________________                                     Skin Score of                                Compound                                                                            Formula (Ie)               conduc-                                                                            skin                                    No.   R.sup.1                                                                            R.sup.51                                                                           R.sup.31      R.sup.32                                                                         tance                                                                              roughness                               __________________________________________________________________________    Invention Product 1                                                           Ie.sub.1                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                Glucopyranosyl                                                                              H  25   1.0                                     Ie.sub.2                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                4-O-β-D-Galacto-                                                                       H  29   0.8                                                     pyranosyl-β-D-                                                           glucopyranosyl                                                Ie.sub.3                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                2-Acetoamino-2-                                                                             H  31   0.7                                                     deoxy-β-D-                                                               glucopyranosyl                                                Ie.sub.4                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                5-Acetamido-3,5-                                                                            H  33   0.5                                                     dideoxy-α-D-                                                            glycero-β-D-galacto-                                                     2-nonuropyranosyl                                             Ie.sub.5                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                 ##STR47##    H  15   1.5                                     Ie.sub.6                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                 ##STR48##    H  16   1.2                                     Ie.sub.5                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                 ##STR49##    H  18   1.2                                     __________________________________________________________________________

                                      TABLE 1-6                                   __________________________________________________________________________                                                       Skin  Score of             Compound                                                                            Formula (Ie)                                 conduc-                                                                             skin                 No.   R.sup.1                                                                            R.sup.51                                                                           R.sup.31            R.sup.32       tance roughness            __________________________________________________________________________    Invention Product 1                                                           Ie.sub.8                                                                            n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                 ##STR50##          H              15    1.4                  Ie.sub.9                                                                            n-C.sub.17 H.sub.35                                                                n-C.sub.14 H.sub.29                                                                 ##STR51##          H              18    1.1                  Ie.sub.10                                                                           n-C.sub.9 H.sub.19                                                                 n-C.sub.10 H.sub.21                                                                 ##STR52##          H              11    1.8                  Ie.sub.11                                                                           i-C.sub.17 H.sub.35                                                                i-C.sub.18 H.sub.37                                                                 ##STR53##          H              16    1.3                  Ie.sub.12                                                                           n-C.sub.17 H.sub.35                                                                Oleyl                                                                               ##STR54##          H              13    1.6                  Ie.sub.13                                                                           n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                H                                                                                                  ##STR55##     11    1.7                  Ie.sub.14                                                                           n-C.sub.15 H.sub.31                                                                n-C.sub.16 H.sub.33                                                                 ##STR56##                                                                                         ##STR57##     10    1.9                  __________________________________________________________________________

                                      TABLE 1-7                                   __________________________________________________________________________                                  Skin Score of                                   Compound    Formula (II)      conduc-                                                                            skin                                       No.         R.sup.6                                                                            R.sup.7                                                                            R.sup.8 tance                                                                              roughness                                  __________________________________________________________________________    Invention                                                                           II.sub.1                                                                            n-C.sub.16 H.sub.33                                                                n-C.sub.16 H.sub.33                                                                --CH.sub.2 CH.sub.2 OH                                                                18   1.0                                        Product 1                                                                           II.sub.2                                                                            n-C.sub.10 H.sub.21                                                                n-C.sub.10 H.sub.21                                                                --CH.sub.2 CH.sub.2 OH                                                                 8   1.6                                              II.sub.3                                                                            n-C.sub.10 H.sub.21                                                                n-C.sub.18 H.sub.37                                                                --CH.sub.2 CH.sub.2 OH                                                                11   1.4                                              II.sub.4                                                                            n-C.sub.18 H.sub.37                                                                n-C.sub.18 H.sub.37                                                                --CH.sub.2 CH.sub.2 OH                                                                21   0.9                                              II.sub.5                                                                            n-C.sub.16 H.sub.33                                                                n-C.sub.16 H.sub.33                                                                --CH.sub.2 COOH                                                                       17   1.0                                              II.sub.6                                                                            n-C.sub.10 H.sub.21                                                                n-C.sub.10 H.sub.21                                                                --CH.sub.2 COOH                                                                        7   1.5                                              II.sub.7                                                                            n-C.sub.10 H.sub.21                                                                n-C.sub.18 H.sub.37                                                                --CH.sub.2 COOH                                                                       10   1.3                                              II.sub.8                                                                            n-C.sub.18 H.sub.37                                                                n-C.sub.18 H.sub.37                                                                --CH.sub.2 COOH                                                                       20   0.9                                              II.sub.9                                                                            n-C.sub.16 H.sub.33                                                                n-C.sub.16 H.sub.33                                                                --COCH.sub.3                                                                          17   1.1                                              II.sub.10                                                                           n-C.sub.10 H.sub.21                                                                n-C.sub.10 H.sub.21                                                                --COCH.sub.3                                                                           9   1.7                                              II.sub.11                                                                           n-C.sub.10 H.sub.21                                                                n-C.sub.18 H.sub.37                                                                --COCH.sub.3                                                                          12   1.5                                              II.sub.12                                                                           n-C.sub.18 H.sub.37                                                                n-C.sub.18 H.sub.37                                                                --COCH.sub.3                                                                          20   1.0                                        Comparative Product 1          6   2.8                                        __________________________________________________________________________

EXAMPLE 2

Using separately the compounds used in Example 1, external skin carepreparations (emulsified cosmetic preparations) of their correspondingcompositions shown below in Table 2 were formulated. Their effects forthe improvement of skin roughness were evaluated in the same manner asin Example 1. Results are shown in Table 3.

                                      TABLE 2                                     __________________________________________________________________________                     (wt. %)                                                      Emulsified cosmetic preparation                                                                Invention product                                                                            Comparative product                           Composition      2    3    4    2    3    4                                   __________________________________________________________________________    Glyceryl ether [in formula (VII),                                                              2.0  --   --   2.0  --   --                                  R is represented by formula (VIII)]                                           Arginine monocetylphosphate                                                                    --   2.0  --   --   2.0  --                                  Polyoxyethylene (20) sorbitan                                                                  --   --   1.0  --   --   1.0                                 stearate                                                                      Sorbitan monostearate                                                                          --   --   1.0  --   --   1.0                                 2-Octyldodecyl myristate                                                                       10.0 10.0 10.0 10.0 10.0 10.0                                Vaseline         3.0  3.0  3.0  3.0  3.0  3.0                                 Squalane         5.0  5.0  5.0  5.0  5.0  5.0                                 Tocopherol acetate                                                                             0.5  0.5  0.5  0.5  0.5  0.5                                 Compound (I or II)                                                                             1.0  1.0  1.0  --   --   --                                  Water            Balance                                                                            Balance                                                                            Balance                                                                            Balance                                                                            Balance                                                                            Balance                             __________________________________________________________________________

                  TABLE 3-1                                                       ______________________________________                                                    Score of skin roughness                                           Invention product                                                                           2            3     4                                            ______________________________________                                        Compound Ia.sub.1                                                                           0.2          0.4   0.8                                          Compound Ia.sub.2                                                                           0.3          0.5   1.0                                          Compound Ia.sub.3                                                                           0.7          1.0   1.3                                          Compound Ia.sub.4                                                                           0.5          0.7   1.1                                          Compound Ia.sub.5                                                                           0.3          0.5   1.0                                          Compound Ia.sub.6                                                                           0.1          0.3   0.7                                          Compound Ia.sub.7                                                                           0.6          0.9   1.2                                          Compound Ia.sub.8                                                                           0.5          0.7   1.1                                          Compound Ia.sub.9                                                                           0.2          0.4   0.9                                          Compound Ia.sub.10                                                                          0.1          0.3   0.6                                          Compound Ia.sub.11                                                                          0.3          0.5   0.8                                          Compound Ia.sub.12                                                                          0.3          0.5   0.9                                          Compound Ia.sub.13                                                                          0.5          0.7   1.1                                          Compound Ia.sub.14                                                                          0.1          0.3   0.6                                          Compound Ia.sub.15                                                                          0.5          0.7   1.0                                          Compound Ia.sub.16                                                                          0.4          0.6   0.9                                          Compound Ia.sub.17                                                                          0.2          0.4   0.7                                          Compound Ib.sub.1                                                                           0.1          0.2   0.7                                          Compound Ib.sub.2                                                                           0.8          1.0   1.2                                          Compound Ib.sub.3                                                                           0.6          0.9   1.1                                          Compound Ib.sub.4                                                                           0.4          0.6   0.9                                          Compound Ib.sub.5                                                                           0.2          0.4   0.8                                          ______________________________________                                    

                  TABLE 3-2                                                       ______________________________________                                                    Score of skin roughness                                           Invention product                                                                           2            3     4                                            ______________________________________                                        Compound Ic.sub.1                                                                           0.7          0.9   1.2                                          Compound Ic.sub.2                                                                           0.6          0.8   1.1                                          Compound Ic.sub.3                                                                           1.0          1.3   1.6                                          Compound Ic.sub.4                                                                           0.8          1.0   1.3                                          Compound Ic.sub.5                                                                           0.8          1.0   1.3                                          Compound Ic.sub.6                                                                           0.9          1.2   1.5                                          Compound Ic.sub.7                                                                           0.6          0.8   1.1                                          Compound Ic.sub.8                                                                           0.4          0.6   0.9                                          Compound Ic.sub.9                                                                           0.5          0.7   1.0                                          Compound Ic.sub.10                                                                          0.6          0.8   1.1                                          Compound Ic.sub.11                                                                          0.8          1.0   1.3                                          Compound Ic.sub.12                                                                          1.0          1.3   1.6                                          Compound Ic.sub.13                                                                          1.1          1.4   1.7                                          Compound Id.sub.1                                                                           0.2          0.4   0.7                                          Compound Id.sub.2                                                                           0.3          0.5   0.8                                          Compound Id.sub.3                                                                           0.5          0.8   1.1                                          Compound Id.sub.4                                                                           0.3          0.5   0.8                                          Compound Id.sub.5                                                                           0.1          0.3   0.6                                          ______________________________________                                    

                  TABLE 3-3                                                       ______________________________________                                                    Score of skin roughness                                           Invention product                                                                           2            3     4                                            ______________________________________                                        Compound Ie.sub.1                                                                           0.4          0.6   0.9                                          Compound Ie.sub.2                                                                           0.4          0.5   0.8                                          Compound Ie.sub.3                                                                           0.3          0.4   0.7                                          Compound Ie.sub.4                                                                           0.2          0.2   0.4                                          Compound Ie.sub.5                                                                           0.7          0.9   1.2                                          Compound Ie.sub.6                                                                           0.8          0.9   1.4                                          Compound Ie.sub.7                                                                           0.5          0.7   1.0                                          Compound Ie.sub.8                                                                           0.6          1.1   1.3                                          Compound Ie.sub.9                                                                           0.6          0.6   1.0                                          Compound Ie.sub.10                                                                          1.0          1.2   1.8                                          Compound Ie.sub.11                                                                          0.7          0.8   1.1                                          Compound Ie.sub.12                                                                          0.9          0.9   1.5                                          Compound Ie.sub.13                                                                          0.9          1.1   1.5                                          Compound Ie.sub.14                                                                          1.2          1.4   1.9                                          ______________________________________                                    

                  TABLE 3-4                                                       ______________________________________                                                      Score of skin roughness                                                       2        3     4                                                ______________________________________                                        Invention product                                                             Compound II.sub.1                                                                             0.1        0.3   0.8                                          Compound II.sub.2                                                                             0.8        1.0   1.2                                          Compound II.sub.3                                                                             0.5        0.8   1.1                                          Compound II.sub.4                                                                             0.1        0.3   0.7                                          Compound II.sub.5                                                                             0.2        0.4   0.8                                          Compound II.sub.6                                                                             0.8        1.0   1.2                                          Compound II.sub.7                                                                             0.5        0.8   1.1                                          Compound II.sub.8                                                                             0.2        0.4   0.8                                          Compound II.sub.9                                                                             0.1        0.3   0.9                                          Compound II.sub.10                                                                            0.8        1.1   1.2                                          Compound II.sub.11                                                                            0.4        0.8   1.2                                          Compound II.sub.12                                                                            0.2        0.4   0.8                                          Comparative product                                                                           2.1        2.5   2.6                                          ______________________________________                                    

EXAMPLE 3 Cosmetic Emulsion

A cosmetic emulsion was formulated in accordance with thebelow-described composition. The water-phase components were maintainedat 70° C. while mixing them under heat. On the side, the oil-phasecomponents were heated and mixed at 80° C. After adding theabove-mentioned water-phase components gradually under stirring to theoil-phase components, the resultant mixture was emulsified uniformly bya homomixer. Subsequent to the emulsification, the mixture was cooleddown to 30° C. by a heat exchanger to obtain the cosmetic emulsion.

    ______________________________________                                                             (wt. %)                                                  ______________________________________                                        Oil-phase components:                                                         Compound IIl           1.0                                                    Microcrystalline wax   0.5                                                    Bees wax               2.0                                                    Lanolin                1.5                                                    Liquid paraffin        30.0                                                   Sorbitan sesquioleate  4.0                                                    Polyoxyethylenesorbitan monooleate                                                                   1.0                                                    (20 E.O.)                                                                     Aluminum stearate      0.2                                                    Butyl paraben          0.1                                                    Water-phase components:                                                       Glycerin               8.0                                                    Methyl paraben         0.3                                                    Perfume base           0.1                                                    Purified water         Balance                                                ______________________________________                                    

EXAMPLE 4 Cleansing Cream

A cleansing creams was formulated in accordance with the below-describedcomposition. The oil-phase components were maintained at 80° C. whilemixing them under heat. The water-phase components which had been heatedand mixed at 70° C. on the side where added to the above-mentioned oilphase components, and the resultant mixture was then emulsifieduniformly by a homogenizer. Subsequent to the emulsification, themixture was cooled down to 30° C. by a heat exchanger to obtain thecleansing cream.

    ______________________________________                                                             (wt. %)                                                  ______________________________________                                        Oil-phase components:                                                         Compound II.sub.1      3.0                                                    Paraffin               2.0                                                    Cetanol                1.0                                                    Vaseline               18.5                                                   Liquid paraffin        28.0                                                   Glycerin monostearate polyoxyethylene                                                                3.0                                                    monolaurate (20 E.O.)                                                         Water-phase components:                                                       Propylene glycol       3.0                                                    Glycerin               2.0                                                    Methyl paraben         0.3                                                    Perfume base           0.1                                                    Purified water         Balance                                                ______________________________________                                    

EXAMPLE 5 Toilet Water

A toilet water was formulated in accordance with the below-describedcomposition. Glycerin and propylene glycol were added to purified water.The former components were dissolved in the latter at room temperatureto obtain a purified water portion. On the other hand, emollient and thesurfactant, antiseptic and perfume base were added to ethanol, and theformer components were dissolved in the latter at room temperature. Thethus-formed solution was added to the above-mentioned purified waterportion to solubilize the former. The resultant solution was modified incolor with a dye and then filtered to obtain the toilet water.

    ______________________________________                                                               (wt. %)                                                ______________________________________                                        Moisturizers:                                                                              Glycerin        5.0                                                           Propylene glycol                                                                              4.0                                              Emollient:   Compound II.sub.2                                                                             0.1                                              Surfactant:  Polyoxyethylene hydro-                                                                        1.0                                                           genated castor oil                                                            (40 E.O.)                                                        Ethanol                      10.0                                             Antiseptic:  Methyl paraben  0.2                                              Purified water               Balance                                          ______________________________________                                    

EXAMPLE 6 Lip Stick

A lip stick was prepared in accordance with the below-describedcomposition. Base materials were heated and molten, and were then mixeduniformly. A color was added to the melt. After kneading the resultantmixture and dispersing the color evenly, the mixture was molten againand a perfume base was added. The melt was defoamed and poured into amold. The mold was cooled quickly to solidify the melt. Thethus-solidified stick was taken out of the mold and filled in adispenser. After straightening up the external appearance of the stickfurther, it was caused to pass through a flame (flaming) whereby itssurface was rendered uniform to obtain the lip stick.

    ______________________________________                                                          (wt. %)                                                     ______________________________________                                        Base materials:                                                               Compound II.sub.3   5.0                                                       Castor oil          45.0                                                      Hexadecyl alcohol   23.0                                                      Lanolin             4.0                                                       Bees wax            5.0                                                       Ozocerite           4.0                                                       Candelilla wax      4.0                                                       Carnauba wax        2.0                                                       Tocopherol          0.1                                                       Butyl paraben       0.1                                                       Colors:                                                                       Titanium oxide      2.0                                                       Red Color No. 202   0.5                                                       Red Color No. 204   2.5                                                       Red Color No. 227 (Al rake)                                                                       2.5                                                       Orange Color No. 201                                                                              0.2                                                       Perfume base        0.1                                                       ______________________________________                                    

EXAMPLE 7 Emulsion-Type Foundation

An emulsion-type foundation was formulated in accordance with thebelow-described composition. The oil-phase components were mixed, heatedand molten, and maintained at 80° C. On the other hand, the powderycomponents were added to and dispersed in the water-phase components.The resultant dispersion was heated to 70° C. The above oil-phasecomponents were added to the water-phase components, followed byemulsification and dispersion by an emulsifying machine. An emulsionthus obtained was cooled down to 30° C. by a heat exchanger to obtainthe emulsion-type foundation.

    ______________________________________                                                          (wt. %)                                                     ______________________________________                                        Oil-phase components:                                                         Compound II.sub.4   3.0                                                       Stearic acid        5.0                                                       Cetostearyl alcohol 1.0                                                       Jojoba oil          15.0                                                      Glycerin monostearate                                                                             2.0                                                       Propylene glycol monolaurate                                                                      3.0                                                       Water-phase components:                                                       Propylene glycol    4.0                                                       Triethanolamine     1.2                                                       Methyl paraben      0.3                                                       Perfume base        0.1                                                       Purified water      Balance                                                   Powdery components:                                                           Titanium oxide      8.0                                                       Talc                4.0                                                       Iron oxide          0.5                                                       ______________________________________                                    

EXAMPLE 8 Hair Tonic

A hair tonic was formulated in accordance with the below-describedcomposition.

    ______________________________________                                                             (wt. %)                                                  ______________________________________                                        Compound II.sub.2      0.2                                                    Menthol                0.2                                                    Pilocton auramine (antidandruff agent)                                                               0.1                                                    Methyl nicotinate      0.1                                                    Ethanol                50.0                                                   Purified water         Balance                                                ______________________________________                                    

EXAMPLE 9

A cosmetic emulsion was obtained in the same manner as in Example 3except that Compound II₉ was used in place of Compound II₁.

EXAMPLE 10

A cleansing cream was obtained in the same manner as in Example 4 exceptthat Compound II₉ was used instead of Compound II₁.

EXAMPLE 11

A toilet water was obtained in the same manner as in Example 5 exceptthat Compound II₁₀ was used in lieu of Compound II₂.

EXAMPLE 12

A lip stick was obtained in the same manner as in Example 6 except thatCompound II₁₁ was used in lieu of Compound II₃.

EXAMPLE 13

An emulsion-type foundation was obtained in the same manner as inExample 7 except that Compound II₁₂ was used instead of Compound II₄.

EXAMPLE 14

A hair tonic was obtained in the same manner as in Example 8 except thatCompound II₁₀ was used in lieu of Compound II₂.

EXAMPLE 15 Cosmetic Emulsion

In accordance with the below-described composition, the oil-phasecomponents were mixed, heated and molten, and maintained at 70° C. Thewater-phase components were also mixed, heated and molten at 70° C. Theabove oil-phase components were added to the water-phase components,followed by emulsification by an emulsifying machine. An emulsion thusobtained was cooled down to a final temperature of 30° C. by a heatexchanger to obtain a cosmetic emulsion.

    ______________________________________                                                           (wt. %)                                                    ______________________________________                                        Oil-phase components:                                                         Cetanol              0.5                                                      Vaseline             3.0                                                      Compound II.sub.5    5.0                                                      Polyoxyethylene (10) monooleate                                                                    2.0                                                      Stearic acid         2.0                                                      Water-phase components:                                                       1,3-Butylene glycol  3.0                                                      Dipropylene glycol   6.0                                                      Triethanolamine      1.0                                                      Ethyl paraben        0.1                                                      Methyl paraben       0.2                                                      Perfume base         0.1                                                      Purified water       Balance                                                  ______________________________________                                    

EXAMPLE 16 Emulsion-Type Foundation

In accordance with the below-described composition, the oil-phasecomponents were mixed, heated and molten, and maintained at 70° C. Onthe other hand, the powdery components were added to and dispersed inthe water-phase components. The resultant dispersion was heated to 70°C. The above oil-phase components were added to the water-phasecomponents, followed by emulsification and dispersion by an emulsifyingmachine. An emulsion thus obtained was cooled down to a finaltemperature of 30° C. by a heat exchanger and was then filled in acontainer, whereby the emulsion-type foundation was obtained.

    ______________________________________                                                          (wt. %)                                                     ______________________________________                                        Oil-phase components:                                                         Stearic acid        5.0                                                       Cetostearyl alcohol 1.0                                                       Olive oil           15.0                                                      Compound II.sub.5   3.0                                                       Glycerin monostearate                                                                             2.0                                                       Propylene glycol monolaurate                                                                      3.0                                                       Water-phase components:                                                       Propylene glycol    4.0                                                       Triethanolamine     1.2                                                       Ethyl paraben       0.1                                                       Methyl paraben      0.2                                                       Perfume base        0.1                                                       Purified water      Balance                                                   Powdery components:                                                           Titanium oxide      8.0                                                       Talc                4.0                                                       Iron oxide          0.5                                                       ______________________________________                                    

EXAMPLE 17 Lip Stick

In accordance with the below-described composition, a lip stick wasobtained by heating and melting microcrystalline wax, candelilla wax,caster oil, Compound II₅, jojoba oil, olive oil and lanolin at 90°-100°C., adding the pigment to the melt, stirring the resultant mixture todisperse the pigment, deaerating the the thus-pigmented mixture, addingthe perfume base to the thus-deaerated mixture, pouring it into a stickmold, cooling the mold to 15°-20° C. and then taking the resultant lipstick out of the mold.

    ______________________________________                                                        (wt. %)                                                       ______________________________________                                        Microcrystalline wax                                                                            6.0                                                         Candelilla wax    3.0                                                         Castor oil        40.0                                                        Compound II.sub.5 8.0                                                         Jojoba oil        6.0                                                         Lanolin           10.0                                                        Olive oil         Balance                                                     Pigment           7.0                                                         Perfume Base      0.1                                                         ______________________________________                                    

EXAMPLE 18 W/O Type Massage Cream

In accordance with the below-described composition, soap powder wasadded to purified water, and the resultant mixture was heated to andmaintained at 70° C. The oil-phase components were mixed, and thenheated to and maintained at 70° C. The above water-phase portion wasadded to the oil-phase portion, followed by provisional emulsification.The resultant mixture was thereafter emulsified evenly by a homomixer,followed by cooling to room temperature or so by a heat exchanger.

    ______________________________________                                                            (wt. %)                                                   ______________________________________                                        Oil-phase components:                                                         Paraffin              4.0                                                     Microcrystalline wax  6.0                                                     Bees wax              6.0                                                     Vaseline              10.0                                                    Compound II.sub.8     4.0                                                     Liquid paraffin       40.0                                                    Sorbitan sesquioleate 3.5                                                     Polyoxyethylene sorbitan monooleate                                                                 0.5                                                     (20 E.O.)                                                                     Water-phase components:                                                       Ethyl paraben         0.1                                                     Methyl paraben        0.2                                                     Tocopheryl acetate    0.5                                                     Soap powder           0.3                                                     Purified water        Balance                                                 ______________________________________                                    

EXAMPLE 19 Pack (Peel-Off Type)

In accordance with the below-described composition, the water-phasecomponents were mixed, heated and molten, and maintained at 70° C.Similarly, the oil-phase components were heated to and mixed at 70° C.The oil-phase components were added to the above water-phase components,and the resultant mixture was emulsified by an emulsifying machine. Thepowdery components and film-forming agent were added to and mixed withthe emulsion. The resultant emulsion was cooled down to a finaltemperature of 30° C. by a heat exchanger and then filled in acontainer, whereby a pack was obtained.

    ______________________________________                                                             (wt. %)                                                  ______________________________________                                        Oil-phase components:                                                         Squalane               2.0                                                    Compound II.sub.6      1.0                                                    Hydrophobic glycerin monostearate                                                                    1.0                                                    polyoxyethylene sorbitan monolaurate                                          (20 E.O.)                                                                     Water-phase components:                                                       Glycerin               3.0                                                    Propylene glycol       3.0                                                    Veegum                 1.0                                                    Purified water         Balance                                                Ethanol                7.0                                                    Powdery components:                                                           Titanium oxide         10.0                                                   Kaolin                 3.0                                                    Film-forming agent:                                                           Polyvinyl alcohol      10.0                                                   Perfume base           0.5                                                    Antiseptic             0.1                                                    ______________________________________                                    

EXAMPLE 20 Hair Tonic

The following components were heated to and dissolved at 70° C., andwere then cooled to obtain a hair tonic.

    ______________________________________                                                             (wt. %)                                                  ______________________________________                                        Compound II.sub.7      0.2                                                    Menthol                0.2                                                    Pilocton auramine (antidandruff agent)                                                               0.1                                                    Methyl nicotinate      0.1                                                    Ethanol                45.0                                                   Purified water         Balance                                                ______________________________________                                    

All the external skin care preparations obtained in Examples 3-20 werehighly effective for the improvement of skin roughness and exhibitedsuperb moistening ability.

We claim:
 1. An external skin care preparation comprising (a) a compound represented by the following formula (II), or a salt thereof: ##STR58## wherein R⁶ and R⁷ mean individually an aliphatic hydrocarbon group having 10-26 carbon atoms and R⁸ denotes a group --CH₂ CH₂ OH, --CH₂ COOH or --COCH₃, and(b) at least one member selected from the group consisting of a surfactant, a plant oil, an animal oil, a synthetic oil, a fatty acid, a glyceride, an analgesic, an antiphlogistic, an antipruritic, a disinfectant, an astringent, an emollient, a hormone, a moisturizer, an ultraviolet absorbent, an alcohol, a chelating agent, a pH regulator, an antiseptic, a thickener, a pigment, and a perfume. 